Glaucoma is an ocular disease having the characteristic of a visual functional disorder which causes a transient or permanent visual field defect and decreased vision. This is derived from that since an aqueous humor is accumulated by a circulatory disorder of an aqueous humor, and an intraocular pressure is continuously increased, an optic nerve is compressed. Decrease in an intraocular pressure is effective for treatment of glaucoma and, in order to decrease an intraocular pressure, for example, drug treatment (eye drops, internal remedy, infusion treatment), laser treatment, or operation treatment is performed.
Previously, among prostaglandins (PGs) which are physiologically active substances, as those that decrease an intraocular pressure, PGFs and PGIs are known. Development of a drug for treating glaucoma or ocular hypertension is being progressed using derivatives of them, and there are some drugs which are actually sold (e.g. latanoprost etc.). However, the existing glaucoma treating drug alone is insufficient in intraocular pressure lowering action and sustainability of drug efficacy and, in at site of glaucoma treatment, since administration at a frequent time or a high concentration, or therapy of joint use of drugs having different mechanisms of action are being performed seeking stronger intraocular pressure lowering action, manifestation of side effects is feared. For this reason, drugs having stronger and sustaining intraocular pressure lowering action, and high safety are desired.
Meanwhile, as the prior art of the present invention compound, the following PG derivatives are exemplified.
As a PG derivative having a bicyclic skeleton, for example, a compound of the general formula (a):
(wherein,
is
etc., La is —(CH2)da—C(R2a)2— (wherein da is 0 to 5, and R2as are hydrogen, methyl or fluoro, and are the same or different) etc., Qa is an oxygen atom etc., R1a is COOR3a (wherein R3a is hydrogen, alkyl of 1 to 12 carbon atoms etc.) etc., R4a is:
(wherein R5a and R6a are hydrogen, alkyl of 1 to 4 carbon atoms or fluoro, and are the same or different, Za is an oxygen atom etc., Ta is alkyl of 1 to 4 carbon atoms, fluoro, chloro etc., and sa is 0 to 3) etc., Va is a valence bond or —CH2, Wa is —(CH2)h, h is 1 or 2, Xa is trans-CH═CH— etc. (a part of definitions of groups was extracted) is known (see Patent Literature 1).
In addition, a compound represented by the general formula (b):
(wherein Lb represents —(CH2)db—(wherein db represents 1 to 5) etc., Q2b represents O etc., R1b represents —COOR19b (wherein R19b represents a C1-C12 alkyl group or a hydrogen atom etc.) etc., a ring R22b represents:
(wherein R4b represents a hydrogen atom etc.) etc., R25b represents:
(wherein R5b and R6b represent a hydrogen atom etc., Zb represents —O— etc., Tb represents a C1-4 alkyl group, fluorine, chlorine, trifluoromethyl or —OR7b— (wherein R7b represents C1-4 alkyl), sb represents 0, 1, 2 or 3, and Xb represents:
(a part of definitions of groups was extracted)) (see Patent Literature 2) is known.
Further, a process for producing a compound represented by the general formula (c):
(wherein Ac represents a C1-2 alkylene group, Bc represents a C2-6 alkylene group, Xc represents C(O) etc., and Zc represents a C1-4 alkylene group etc. (a part of definitions of groups was extracted)) is known (see Patent Literature 3).
Meanwhile, it has been reported that agonistic activity on an IP receptor among PG receptors causes hyperemia and rise in a aqueous humor protein, and inducement of stimulation on eyes has been feared (see Non-Patent Literatures 1 and 2). For this reason, since the compound described in Patent Literature 2 which is a PGI2 derivative has agonistic activity on an IP receptor, there is a probability that property of stimulating eyes etc. are induced.
Further, it has been also known that agonistic activity on an EP1 receptor among PGE subtype receptors causes itching of eyes (see Non-Patent Literature 3).
The present invention compound is a compound which has low agonistic activity on an IP receptor and an EP1 receptor, and has selective agonistic activity on a FP receptor, but there is neither the description nor the suggestion regarding such the characteristic (selectivity) in any prior arts.